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Pathway Analysis of Fucoidan Activity Using a Yeast Gene Deletion Library Screen

Fucoidan, the sulfated fucose-rich polysaccharide derived from brown macroalgae, was reported to display some anti-cancer effects in in vitro and in vivo models that included apoptosis and cell cycle arrest. The proposed mechanisms of action involve enhanced immune surveillance and direct pro-apopto...

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Autores principales: Corban, Monika, Ambrose, Mark, Pagnon, Joanne, Stringer, Damien, Karpiniec, Sam, Park, Ahyoung, Eri, Raj, Fitton, J Helen, Gueven, Nuri
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6356313/
https://www.ncbi.nlm.nih.gov/pubmed/30646537
http://dx.doi.org/10.3390/md17010054
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author Corban, Monika
Ambrose, Mark
Pagnon, Joanne
Stringer, Damien
Karpiniec, Sam
Park, Ahyoung
Eri, Raj
Fitton, J Helen
Gueven, Nuri
author_facet Corban, Monika
Ambrose, Mark
Pagnon, Joanne
Stringer, Damien
Karpiniec, Sam
Park, Ahyoung
Eri, Raj
Fitton, J Helen
Gueven, Nuri
author_sort Corban, Monika
collection PubMed
description Fucoidan, the sulfated fucose-rich polysaccharide derived from brown macroalgae, was reported to display some anti-cancer effects in in vitro and in vivo models that included apoptosis and cell cycle arrest. The proposed mechanisms of action involve enhanced immune surveillance and direct pro-apoptotic effects via the activation of cell signaling pathways that remain largely uncharacterized. This study aimed to identify cellular pathways influenced by fucoidan using an unbiased genetic approach to generate additional insights into the anti-cancer effects of fucoidan. Drug–gene interactions of Undaria pinnatifida fucoidan were assessed by a systematic screen of the entire set of 4,733 halpoid Saccharomyces cerevsiae gene deletion strains. Some of the findings were confirmed using cell cycle analysis and DNA damage detection in non-immortalized human dermal fibroblasts and colon cancer cells. The yeast deletion library screen and subsequent pathway and interactome analysis identified global effects of fucoidan on a wide range of eukaryotic cellular processes, including RNA metabolism, protein synthesis, sorting, targeting and transport, carbohydrate metabolism, mitochondrial maintenance, cell cycle regulation, and DNA damage repair-related pathways. Fucoidan also reduced clonogenic survival, induced DNA damage and G1-arrest in colon cancer cells, while these effects were not observed in non-immortalized human fibroblasts. Our results demonstrate global effects of fucoidan in diverse cellular processes in eukaryotic cells and further our understanding about the inhibitory effect of Undaria pinnatifida fucoidan on the growth of human cancer cells.
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spelling pubmed-63563132019-02-05 Pathway Analysis of Fucoidan Activity Using a Yeast Gene Deletion Library Screen Corban, Monika Ambrose, Mark Pagnon, Joanne Stringer, Damien Karpiniec, Sam Park, Ahyoung Eri, Raj Fitton, J Helen Gueven, Nuri Mar Drugs Communication Fucoidan, the sulfated fucose-rich polysaccharide derived from brown macroalgae, was reported to display some anti-cancer effects in in vitro and in vivo models that included apoptosis and cell cycle arrest. The proposed mechanisms of action involve enhanced immune surveillance and direct pro-apoptotic effects via the activation of cell signaling pathways that remain largely uncharacterized. This study aimed to identify cellular pathways influenced by fucoidan using an unbiased genetic approach to generate additional insights into the anti-cancer effects of fucoidan. Drug–gene interactions of Undaria pinnatifida fucoidan were assessed by a systematic screen of the entire set of 4,733 halpoid Saccharomyces cerevsiae gene deletion strains. Some of the findings were confirmed using cell cycle analysis and DNA damage detection in non-immortalized human dermal fibroblasts and colon cancer cells. The yeast deletion library screen and subsequent pathway and interactome analysis identified global effects of fucoidan on a wide range of eukaryotic cellular processes, including RNA metabolism, protein synthesis, sorting, targeting and transport, carbohydrate metabolism, mitochondrial maintenance, cell cycle regulation, and DNA damage repair-related pathways. Fucoidan also reduced clonogenic survival, induced DNA damage and G1-arrest in colon cancer cells, while these effects were not observed in non-immortalized human fibroblasts. Our results demonstrate global effects of fucoidan in diverse cellular processes in eukaryotic cells and further our understanding about the inhibitory effect of Undaria pinnatifida fucoidan on the growth of human cancer cells. MDPI 2019-01-14 /pmc/articles/PMC6356313/ /pubmed/30646537 http://dx.doi.org/10.3390/md17010054 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Communication
Corban, Monika
Ambrose, Mark
Pagnon, Joanne
Stringer, Damien
Karpiniec, Sam
Park, Ahyoung
Eri, Raj
Fitton, J Helen
Gueven, Nuri
Pathway Analysis of Fucoidan Activity Using a Yeast Gene Deletion Library Screen
title Pathway Analysis of Fucoidan Activity Using a Yeast Gene Deletion Library Screen
title_full Pathway Analysis of Fucoidan Activity Using a Yeast Gene Deletion Library Screen
title_fullStr Pathway Analysis of Fucoidan Activity Using a Yeast Gene Deletion Library Screen
title_full_unstemmed Pathway Analysis of Fucoidan Activity Using a Yeast Gene Deletion Library Screen
title_short Pathway Analysis of Fucoidan Activity Using a Yeast Gene Deletion Library Screen
title_sort pathway analysis of fucoidan activity using a yeast gene deletion library screen
topic Communication
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6356313/
https://www.ncbi.nlm.nih.gov/pubmed/30646537
http://dx.doi.org/10.3390/md17010054
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